Find a new factor controlling ovarian function and Elucidating the mechanism of luteal dysfunction
| Project/Area Number |
16591640
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Gunma University |
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Principal Investigator |
NAKAMURA Kazuto GUNMA UNIVERSITY, Medicine, LECTURER, 大学院・医学系研究科, 講師 (60332558)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | LH receptor / FSH receptor / splice variant / betaglycan / サブトラクションクローニング |
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| Research Abstract |
In the corpus luteum of women with a normal menstrual cycle, the wild type of LH receptor (LHR) and the splice variant receptor lacking exon 9 【LHR(exon 9)】, were detected. Since the functional analysis of LHR(exon 9) could not performed in vivo, in vitro studies were designed : the expression vector containing LHR and LHR(exon 9), respectively was transfected into 293 cells. It was demonstrated that LHR(exon 9) attenuated the expression of FSH receptor (FSHR) as well as LHR at the cell surface. The underlying mechanism was proposed as the association of LHR(exon 9) with FSHR or LHR translocated the receptor complexes to the lysosome instead of the plasma membrane, thereby the receptor complex was eventually degraded. Moreover, the expression pattern of LHR(exon 9) was studied, suggesting that LHR(exon 9) expression could be detected from 10 days of menstrual cycle and was elevated to reach a peak level around 20 days of menstrual cycle after ovulation, then declined. Assuming that this receptor association happens in the human ovary, LHR(exon 9) may negatively regulate the FSHR function after ovulation and the LHR function in the late luteal phase.
Furthermore, the functional studies of LHR(exon 9) were conducted, representing that LHR(exon 9) persistently exists inside the cell and never come out to the plasma membrane. It has been generally accepted that protein in the cell, which is translated from mRNA, is subjected to the secondary modification including tertially structure conversion and sugar chain addition. Molecurlar chaperon is supposed to involve in this pathway. During characterization of LHR(exon 9), LHR(exon 9) was shown to significantly reduce the interaction with GRP78.
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Report
(3 results)
Research Products
(9 results)
